Spectroscopic studies (largely multinuclear nuclear magnetic resonance) of the reactive forms of heme enzymes and model porphyrin complexes are proposed to understand the mechanism of action of oxidizing hem enzymes (cytochrome P450, hem oxygenase, peroxidases, ferryl myoglobin). In proteins resonance assignments will be accomplished by isotopic labeling, nuclear Overhauser effects, saturation transfer, 3H-NMR, and 57Fe, and comparison with modes. These will be used to gain information about the structure and reactivity of the heme sites. Model studies for the reactive forms include studies of ferryl (FeIV=0)2+ complexes, porphyrin N-oxide complexes, and iron oxo phlorins. Studies of peroxidases include examination of the heme cavity, substrate-binding, acidic and alkalin forms, probes of propionate interactions, and compound I electronic structure. New methodologies for obtaining NMR spectral information from paramagnetic and diamagnetic forms of cytochrome P-450cam are proposed. Models for the process of covalent porphyrin modification (N-alkylation, oxidative degradation) will be examined especially in terms of the regiospecifity of transfer of substituents from iron to pyrrole group or meso positions in unsymmetrical hemes. Extensive studies of the recently detected multiple forms of sulfmyoglobin (formed by sulfide reaction of ferryl myoglobin) are proposed including structural characterization of protein forms and extractable green and red modified porphyrins, studies of the mechanism of formation and interconversion of these forms, preparation of model porphyrins with appended sulfur-containing functional groups, studies of the (FeIV=0)2+/S-2 reaction in models, examination of potential multiple forms sulfhemoglobin and studies of reagents which convert sulfhemes back to their native forms with a view toward clinically useful material for the treatment of sulfhemoglobinanemia.